This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The McLaughlin group's research spans three related areas: (1) they prepare nucleoside analogues as potential antivirals. They examine structural alterations on both the nucleobase as well as the sugar. Their goal is to develop compounds that exhibit differential activity with polymerase - active with the virus, inactive wit human polymerases - this will help to develop new anti-virals. (2) Understanding macromolecular recognition processes is critical to understanding gene expression. To probe such processes, they prepare modified DNA sequences in which the recognition sites are functionally altered. They use these altered DNA sequences to probe structure, function and recognition. (3) The natural structural characteristics of DNA lend themselves to the construction of repeating lattices formed by hybridization of complementary DNA sequences. These nanoscale structures can be used as crystallization scaffolds for multi-component systems, to sequester nanometer sized solutes or for controlled release of nanoscale pharmaceuticals.